TLR9 is a novel therapeutic target for allergic asthma

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15133
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Musashino University
• Principal Investigator: Murakami Yusuke 武蔵野大学, 薬学部, 助教 (50757325)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: Toll-Like Receptor / アレルギー性喘息

Outline of Final Research Achievements

Allergic asthma is a disease that causes dyspnea with a house dust mite-derived component as the main allergen. TLR9 has been reported to exacerbate inflammation in response to not only foreign antigens but also self-derived DNA released by inflammation. Therefore, we analyzed the role of TLR9 in allergic asthma. Then, the pathology was suppressed in the TLR9 gene-deficient mouse. IL-17A production was increased. Therefore, we verified IL-17A. The disease state was suppressed in the IL-17A-administered group. Next, we searched for factors that regulate IL-17A. We identified IL-2 as a negative regulator of IL-17A. It was suggested that the TLR9-IL-2 pathway exacerbates the pathology of allergic asthma.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ヒョウダニは身近なアレルゲンであり、アレルギー性喘息の原因となる。本研究では、ダニ抽出物を用いた喘息モデルで、Toll-like receptor9(TLR9)遺伝子欠損マウスを解析することにより、TLR9-IL-2経路が喘息を悪化させていることが示唆された。この結果は、アレルギー性喘息の新たな病態メカニズムを明らかにするとともに、TLR9を治療標的とする新規治療法の開発につながる可能性がある。